SPREADING DEPRESSION AND REVERBERATORY SEIZURES INDUCE THE UP-REGULATION OF MESSENGER-RNA FOR GLIAL FIBRILLARY ACIDIC PROTEIN

The present study evaluates the relative roles of seizure activity and spreading depression in upregulating glial fibrillary acidic protein (GFAP) mRNA expression. Stimulating electrodes were placed bilaterally in the angular bundle, and recording electrodes were placed bilateral ly in the dentate gyrus of adult rats. Intense electrographic seizures were induced by delivering stimulus trains through one stimulating el ectrode. In some cases, spreading depression accompanied the seizures, while in other cases the seizures occurred in the absence of spreadin g depression. Animals were killed 24 h following the last stimulus tra in, and the forebrains were prepared for quantitative in situ hybridiz ation. Seizure activity and spreading depression led to significant in creases in GFAP mRNA levels in the hippocampal formation. Seizure acti vity alone (without spreading depression) induced a 4-fold increase in GFAP mRNA levels in the hilus and molecular layer of the dentate gyru s and in stratum lacunosum-moleculare of the hippocampus. When seizure activity was accompanied by spreading depression, there was a 10-fold increase in GFAP mRNA levels in these same regions. Regional differen ces within the hippocampal formation in glial cell response were evide nt. While GFAP mRNA levels in stratum lacunosum-moleculare of the hipp ocampus were upregulated by seizure activity and spreading depression, levels in hippocampal stratum radiatum of the hippocampus remained un changed. The results suggest that abnormal neuronal activity can influ ence glial cell gene expression and that spreading depression is a str onger signal than seizure activity in upregulating GFAP mRNA levels.